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Nearly One-third of HIV/HCV Coinfected Patients with Normal ALT Have Liver Fibrosis that Indicates Treatment

SUMMARY: HIV positive individuals coinfected with hepatitis C virus (HCV) are more likely than HCV monoinfected patients to have a degree of liver fibrosis that justifies treatment, even if they have persistently normal alanine aminotransferase (ALT) levels, according to study reported in the November 2009 Journal of Viral Hepatitis.

By Liz Highleyman

Research has shown that HIV positive individuals with chronic hepatitis C -- especially those with advanced immune suppression -- experience more rapid liver disease progression than people with HCV alone, and therefore may benefit from earlier hepatitis C treatment.

In the present study, L. Martin-Carbonero from Hospital Carlos III in Madrid, Spain, and colleagues compared liver fibrosis progression in patients with persistent normal and elevated ALT.

ALT is a liver enzyme released during liver injury. Though often measured as a overall sign of liver health, it is marker of liver inflammation, and may not be a good indicator of fibrosis. Studies of HCV monoinfected individuals have shown that advanced fibrosis can occur with persistently normal ALT, but this has not been extensively studied in HIV/HCV coinfected patients.

This analysis included all previously untreated HCV RNA positive patients with persistently normal ALT who underwent liver fibrosis assessment using transient elastometry (FibroScan) -- a non-invasive method of estimating fibrosis based on liver "stiffness" -- since 2004 at 3 European hospitals; those who had received interferon-based therapy were excluded.

Persistently normal ALT was defined as ALT below the upper limit of normal on at least 3 consecutive measurements within the past 12 months. Fibrosis stage was defined as mild (corresponding to Metavir stage F0-F1) if liver stiffness was <7.1 kiloPascals (kPa), moderate (stage F2) if 7.2-9.4 kPa, severe (stage F3) if 9.5-14 kPa, and cirrhosis (stage F4) if > 14 kPa. Moderate or greater liver fibrosis is generally considered an indication for hepatitis C treatment.

A total of 449 HIV negative and 133 HIV positive patients were evaluated. The HIV negative participants were more likely to be women (63%vs 37%) and were older on average (mean 51.8 vs 43.5 years) than the HIV positive group. About 80% of the HIV patients were on combination antiretroviral therapy and their mean CD4 count was 525 cells/mm3.


Mean serum HCV RNA levels were similar in the HIV negative and HIV positive groups (5.9 vs 5.8 log IU/mL).
Among HIV negative patients, 84.6% had mild liver fibrosis, 8.7% had moderate fibrosis, 3.3% had severe fibrosis, and 3.3% had cirrhosis.
Among HIV positive participants, the corresponding proportions were 70.7%, 18.8%, 6%, and 4.5%, respectively.
Taken together, 6.6% of HCV monoinfected patients and 10.5% of HCV/HIV coinfected patients had severe liver fibrosis or cirrhosis.
In a multivariate analysis, older age (odds ratio [OR] 1.04) and being HIV positive (OR 2.6) were significantly associated with severe liver fibrosis or cirrhosis (stage F3-F4).

Based on these findings, the study authors concluded, "Some degree of liver fibrosis that justifies treatment is seen in 15% of the HCV monoinfected but doubles to nearly 30% in HIV/HCV coinfected patients with persistently normal ALT."

Infectious Diseases Department, Hospital Carlos III, Madrid, Spain; Hepato-Gastroenterology Department, Hôpital Haut-Leveque, Bordeaux, France; Hepatology Unit and CIBEREDH, Hospital Carlos III, Madrid, Spain; Infectious Diseases Department, University of Sassari, Sassari, Italy.


L Martin-Carbonero, V de Ledinghen, A Moreno, and others. Liver fibrosis in patients with chronic hepatitis C and persistently normal liver enzymes: influence of HIV infection. Journal of Viral Hepatitis 16(11): 790-795 (Abstract). November 2009.


























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